Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.
Cytokine. 2022 Sep;157:155951. doi: 10.1016/j.cyto.2022.155951. Epub 2022 Jun 27.
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are the most common severe cutaneous adverse drug reactions (SCARs). Anti-epileptic drugs are one of the most common drugs causing SCARs. Cytokine profiles of SCARs during culprit drug exposure have never been characterized. This study aimed to identify cytokine patterns between SCARs and non-SCARs in epilepsy patients and the patterns of DRESS and SJS/TEN. Epilepsy patients that showed allergic responses to anti-epileptic drugs that manifested as SJS/TEN or DRESS were recruited. Epilepsy patients with no drug allergy symptoms and healthy people were also recruited as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with assigned anti-epileptic drugs according to the lymphocyte transformation test (LTT). LTT and measurement of cytokine levels in supernatants were performed on day six of cell cultivation. This study identified different cytokine expression patterns between SCAR and non-SCAR in epilepsy patients. Significant levels of IL-10, IL-12, IL-17, and GM-CSF were detected in non-SCAR epilepsy. However, the levels of IL-2, IL-5, IL-13, and IFN-gamma were significantly higher in supernatants of PBMCs of DRESS cultivated with AEDs relative to those of SJS/TEN. These cytokine levels were positively correlated with the cell proliferation index. Production of IL-5 and IL-13 was a unique characteristic of DRESS PBMCs. This study was the first to demonstrate distinct differences in cytokine levels between SCAR and non-SCAR PBMCs in epilepsy, which could help explain the immune-pathomechanism of drug hypersensitivity in SCARs. Different patterns of cytokine production and cell proliferation between DRESS and SJS/TEN in AED hypersensitivity were also demonstrated. Production of IL-5 and IL-13 might be a promising marker to define drug hypersensitivity in DRESS.
史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症（SJS/TEN）和伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）是最常见的严重皮肤药物不良反应（SCARs）。抗癫痫药物是引起 SCARs 的最常见药物之一。在引起药物反应的药物暴露期间，SCARs 的细胞因子谱从未被描述过。本研究旨在确定癫痫患者中 SCAR 与非 SCAR 之间的细胞因子模式，以及 DRESS 和 SJS/TEN 的模式。招募了对抗癫痫药物表现出过敏反应的癫痫患者，这些反应表现为 SJS/TEN 或 DRESS。还招募了无药物过敏症状的癫痫患者和健康人作为对照组。分离外周血单核细胞（PBMC），并根据淋巴细胞转化试验（LTT）与指定的抗癫痫药物共培养。在细胞培养的第六天进行 LTT 和上清液中细胞因子水平的测量。本研究确定了癫痫患者中 SCAR 与非 SCAR 之间不同的细胞因子表达模式。在非 SCAR 癫痫患者中检测到 IL-10、IL-12、IL-17 和 GM-CSF 的显著水平。然而，与 SJS/TEN 相比，用 AED 培养的 DRESS 的 PBMCs 上清液中 IL-2、IL-5、IL-13 和 IFN-gamma 的水平显著升高。这些细胞因子水平与细胞增殖指数呈正相关。IL-5 和 IL-13 的产生是 DRESS PBMC 的独特特征。本研究首次证明了癫痫患者中 SCAR 和非 SCAR PBMC 之间细胞因子水平的明显差异，这有助于解释 SCAR 中药物超敏反应的免疫发病机制。还证明了 AED 超敏反应中 DRESS 和 SJS/TEN 之间细胞因子产生和细胞增殖的不同模式。IL-5 和 IL-13 的产生可能是定义 DRESS 中药物超敏反应的有前途的标志物。
